The establishment and maintenance of pregnancy require the appropriate development of a specialized maternal tissue, referred to as decidua. Decidual cells arise from uterine stroma via the actions of progesterone, form intimate relationships with placental structures, and facilitate the development of the embryo. Among the important functions of decidual cells are their hormone/cytokine producing capabilities. Hormone/cytokines related to prolactin (PRL) are prominent decidual cell secretory proteins and include, decidual/trophoblast prolactin-related protein (d/tPRP). The uteroplacental PRL family contributes to the regulation of uterine inflammatory cell responses accompanying pregnancy. D/tPRP has been shown to associate with heparin containing molecules in the extracellular matrix and specifically interact with eosinophils. Eosinophils are a part of the maternal inflammatory response and must be controlled in order to ensure the establishment of pregnancy. We hypothesize that the decidual cell product, d/tPRP, participate in the modulation of maternal adaptations to pregnancy, including mediation of the anti-inflammatory actions of progesterone. In this research project, we propose to investigate decidual cell signaling. In Aim I we propose to identify cellular responses to d/tPRP. Aim 2 focuses on determining mechanisms underlying the interactions of d/tPRP with heparin and eosinophils. Under Aim 3 we examine d/tPRP-eosinophil interactions in vivo. Each Specific Aim is entirely independent and will be started at the beginning of year 1 of the grant period and will proceed in parallel through the end of the proposed grant period. The planned research utilizes cellular and molecular and in vitro and in vivo strategies. Data derived from the proposed experimentation will improve our understanding of the nature of decidua cell signaling and the role of the decidual PRL family in the regulation of viviparity. These findings will provide considerable insight into the etiology of developmental disorders associated with pregnancy failure and will also have important ramifications on our understanding of the control of eosinophil functions in aberrant processes such as immune disease and cancer.